The clinical impact of the 5 million annual surveillance colonoscopies (follow up of previous neoplasia) is remarkably low (>90% without significant neoplasia). Juxtaposed with this is the alarmingly frequent occurrence of colorectal cancers (CRCs) in between colonoscopies (interval cancers), especially in the proximal colon. The medico-legal and clinical consequences of interval CRCs lead to vast overuse of surveillance colonoscopy engendering unnecessary cost, complications etc. Fecal tests represent an attractive potential adjunct although the typical tests (occult blood, DNA, methylation) have a poor (~10-40%) sensitivity for advanced adenomas, the target of CRC prevention efforts. Our multidisciplinary CRC prevention group has developed a mucus layer fecal colonocyte biophotonics test that allows detection of both field carcinogenesis along with the less abundant tumor products. We have employed our ultrasensitive novel technology, partial wave spectroscopic microscopy (PWS). PWS allows, for the first time, a practical modality to quantify nanoscale architectural colonic epithelial alterations in preclinica models (PNAS, 2008). We have demonstrated that colonocyte PWS analysis has a ~90% accuracy of identifying individuals for colonic advanced adenomas throughout the colon (n=141) (Gastro, 2011). In order for Nanocytomics to commercialize fecal PWS for tailoring colonoscopic screening intervals, we propose to develop a high throughput instrument (phase 1) with milestones of accuracy and speed (<10 minutes per patient). Phase 2 will involve clinical trials in two common scenarios: 1. Determine whether a patient scheduled for colonoscopy can be safely postponed (n=200 training and 200 testing set) 2. Investigate whether a patient needs to have an expedited colonoscopy (n=250). These will be compared to conventional fecal tests (immunohistochemical and DNA). These studies will be instrumental to bridge the power of PWS to the clinical application off colonoscopic screening interval personalization thus representing a large and well defined commercial opportunity. Furthermore, identification of field carcinogenesis with PWS is a platform with clear applications for average risk CRC screening along with other cancers (lung, ovarian etc). PUBLIC HEALTH RELEVANCE: CRCs remain the second leading cause of cancer deaths among Americans. Colonoscopy can prevent CRCs by identifying and removing precursor lesions but this often obligates serial examinations. However, follow up colonoscopies (surveillance) are vastly overused and still allow a significant number of cancers to occur. Our goal is to leverage the remarkable sensitivity of the powerful new technology, PWS to develop a highly accurate minimally intrusive fecal test that could enable personalization of the procedure intervals.